Revision Session Organic Chemistry

Stereochemistry and mechanism Starter Past Paper Questions and Answers

Starter Past Paper Questions and Answers Aromaticity Starter Past Paper Questions and Answers

Question 1 (a) Huckel’s Rule Discuss [100%]

Aromatics

Carbonyl Group Chemistry Revision and Past Paper Questions and Answers Carbonyl Group Chemistry

Basic Carbonyl Chemistry Carbonyl acts as both an electrophile and a nucleophile Carbonyl has resonance structure

Basic carbonyl chemistry Electrophile:

Basic carbonyl chemistry Formation of Enolates and Enols Removal of alpha-proton (most acidic)

Basic carbonyl chemistry Enolate Alkylation Nucleophile

Basic carbonyl chemistry Acidities of alpha and beta carbonyl protons

Basic carbonyl chemistry 1,3 – Dicarbonyl Compounds Why is central alpha proton more acidic? Conjugation and intramolecular H – bonding

Basic carbonyl chemisty Alpha substitution reactions Reaction with an electrophile (acid catalysed)

Basic carbonyl chemistry Alpha substitution reactions Reaction with an electrophile (base catalysed)

Basic carbonyl chemistry Bases used for enolate formation Carbonyl compounds weakly acidic Strong base needed to ensure complete enolate formation LDA Lithium diisopropylamide

Basic carbonyl chemistry Deuterium Substitution of alpha protons When enriched with D2O (acid or base), all alpha protons are in equilibria with deuterium Used as an isotopic label in molecules

Basic carbonyl chemistry Racemization Stereochemistry at alpha carbon is lost during enolate formation Protonated unequally at two faces

Basic Carbonyl CHemistry Halogenation of Carbonyls (acid catalysed)

Basic carbonyl chemistry Halogenation of Carbonyls (lewis acid)

Basic carbonyl chemistry Unsymmetrical Ketones Two different enols are formed Occurs preferentially at the more substituted position as more stable

Basic carbonyl chemistry Enolates of Unsymetrical Ketones Kinetic favoured due to unhindered alpha protons

Basic carbonyl chemistry 1,3 – Dicarbonyl Compounds Alkylate at different sites in different conditions

Basic carbonyl chemistry Decarboxylation of beta-ketoesters

Basic carbonyl chemistry Add a -CH2CO2H to an alkyl halide

Basic carbonyl chemistry Add a -CH2COCH3 to an alkyl halide

Basic carbonyl chemistry Add a -CH2CO2H then –COCH3 to an acyl halide

Aldol reaction https://learn.uea.ac.uk/webapps/portal/fram eset.jsp?tab_tab_group_id=_4_1&url=%2Fweba pps%2Fblackboard%2Fexecute%2Flauncher%3Ft ype%3DCourse%26id%3D_85894_1%26url%3D Click Vignettes – Level 1 – Aldol Reaction

Basic carbonyl chemistry Aldol Reaction Mixed Aldol Reaction Use LDA (one equivalent) to convert all of aldehyde to enolate Same Ketone Aldol Reaction Use NaOEt/EtOH to convert a small proportion to enolate

Basic carbonyl chemistry Aldol Dehydration Base Catalysed Acid Catalysed (more common)

Basic carbonyl chemistry Intramolecular Aldol Reactions Dicarbonyl compounds treated with base Leads to cyclic product

Basic carbonyl chemistry Intramolecular Aldol Reactions For Unsymmetrical Dicarbonyl Species more than one product is possible

Basic carbonyl chemistry Claisen Condensation Esters react in same fashion as aldol reaction Intramolecular Claisen Condensations aswell

Basic carbonyl chemistry Knoevenagel Condensation

Basic carbonyl chemistry Michael Reaction Enolates react with conjugated carbonyls through terminus double bonds rather than the carbonyl itself!

Robinson Annelation Micheal reaction followed by intramolecular aldol Micheal Addition Intramolecular Aldol Aldol Condensation (Base catalysed)

Basic carbonyl chemistry Condensation with Amine Derivatives Ketone  Imine

Basic carbonyl chemistry Condensation with Amine Derivatives Imine  Enamine

Basic carbonyl chemistry Enamine Reactivity React simular to enolates in neutral form. Forms iminium salt, hydrolysis leads to alkylated carbonyl

basic carbonyl chemistry Enamine Reactivity

Basic carbonyl chemistry Wittig Reaction Introduces alkenes from ketones using phosphorus ylids.

Wittig reaction Stage 1 Preparation of a phosphonium salt from an alkyl halide

Wittig reaction Stage 2 Deprotonation of the phosphonium salt to form a ylid

Wittig reaction Stage 3 Reaction of the ylid with a carbonyl group

Wittig reaction E or Z alkenes? Ylids that have a conjugating or anion- stablilizing substituent (such as a carbonyl) adjacent to negative charge give E – Alkenes Ylids without such groups are unstabilized ylids and tend to give Z – Alkenes

Wittig reaction Example of Z – Alkene formation Example of E – Alkene formation

Revision and Past Paper Questions and Answers Pericyclic Reactions Revision and Past Paper Questions and Answers

Pericyclic Reactions Pericyclic Reaction: A concerted reaction that takes place as a result of a cyclic rearrangement of electron density Concerted: Bond making and bond breaking takes place at the same time No intermediates are formed, proceeds through a single transition state

Cycloaddition Cycloadditions Diels-Alder Reaction [4+2] cycloaddition (4π + 2π = 6π electrons) Reversible reaction but driven to product due to loss of 2 pi bonds and formation of 2 sigma bonds Diene must be Z (cis)

Stereochemistry of Diels Alder Cycloaddition Stereochemistry of Diels Alder

Stereochemistry of Diels Alder Cycloaddition Stereochemistry of Diels Alder

Hetero Diels-Alder Reactions Cycloaddition Hetero Diels-Alder Reactions Examples

Cycloaddition Other Cycloadditions Example: [8 + 2] Thermal Conditions

Cycloaddition Other Cycloadditions

Cycloaddition Other Cycloadditions How to tell if a cycloaddition under thermal conditions work? If Aromatic Intermediate (4n+2) then yes If Antiaromatic Intermediate (4n) then no [2+2] Antiaromatic No [4+2] Aromatic Yes [4+4] Antiaromatic No [6+4] Aromatic Yes [8+2] Aromatic Yes Etc…

Cycloaddition Photochemical [2+2] By exciting the HOMO to a higher energy state (HOMO*) the phases are changed to allow orbital overlap

Thermal [2+2] Cycloaddition Special Case where photochemical activation is not needed, use Ketene. Why? Central carbon atom is sp hybridised and overlaps antiarafacial

Antarafacial Overlap for Ketene [2+2] Cycloaddition Antarafacial Overlap for Ketene [2+2]

Sigmatropic Rearrangements Sigmatropic Rarrangement Sigmatropic Rearrangements Example [3,3]-sigmatropic rearrangement Driving Force Enol – Keto tautomerisation – C=O stronger than C=C

Claisen Rearrangement Sigmatropic Rarrangement Claisen Rearrangement First sigmatropic rearrangement Phenyl allyl ether is heated to give ortho-substituted phenol

Sigmatropic Rearrangement Sigmatropic Rarrangement Sigmatropic Rearrangement Proceed via a chair-like transition state For Substituted Allyl Ethers (on sp3 next to oxygen) the resulting alkene is always E (trans)!

Sigmatropic Rarrangement Cope Rearrangement Use Carbon instead of oxygen. Note with no substituents; no overall reaction. Again only E (trans) alkenes formed

[2,3]-Sigmatropic Rearrangements Sigmatropic Rarrangement [2,3]-Sigmatropic Rearrangements Proceeds via a 5 membered transition state Requires negative charge for 6 electron movement

[2,3]-Sigmatropic Rearrangements Sigmatropic Rarrangement [2,3]-Sigmatropic Rearrangements Again E (Trans) favoured due to nature of transition state (not going to cover here)

[1,5]-Sigmatropic Hydrogen Shifts Sigmatropic Rarrangement [1,5]-Sigmatropic Hydrogen Shifts

Electrocyclic Reactions Only one sigma bond formed across conjugated system, loss of one pi bond.

Electrocyclic Reactions Exceptions Expect Anti-Aromatic transition state so this should not happen?

Electrocyclic Reactions Nazarov Cyclisation

Carbocation Rearrangements More Alkyl Substituents = More Stable Carbocation will rearrange to give an alternative more thermodynamic cation by adding substituents wherever possible

Carbocation Rearrangements Driven by thermodynamics

Wagner-Meerwein Rearrangements Carbocation Rearrangements

Pinacol Rearrangement Carbocation Rearrangements Pinacol Rearrangement

Choice of Migrating Group Carbocation Rearrangements Choice of Migrating Group

Carbocation Rearrangements Unsymmetrical Diols

Dienone-Phenol Rearrangement Carbocation Rearrangements Dienone-Phenol Rearrangement Again, phenyl has right of way against methyl.

Beckmann Rearrangement Carbocation Rearrangements Beckmann Rearrangement

Beckmann Rearrangement Carbocation Rearrangements Beckmann Rearrangement

Beckmann Rearrangement Carbocation Rearrangements Beckmann Rearrangement

Benzillic Acid Rearrangement Anionic Rearrangements Benzillic Acid Rearrangement Related to Pinacol Rearrangement

Favorskii Rearrangement Anionic Rearrangements Favorskii Rearrangement Similar to Benzillic Acid Rearrangement

Favorskii Rearrangement Anionic Rearrangements Favorskii Rearrangement Ring Contraction method

Baeyer-Villiger Reaction Anionic Rearrangements Baeyer-Villiger Reaction Very Important Migration to Oxygen

Baeyer-Villiger Reaction Anionic Rearrangements Baeyer-Villiger Reaction Preference of Migrating Group The group that is more able to stabilise a positive charge has right of way. Phenyl has right of way due to cyclopropane intermediate Stereochemistry is retained during reaction